1. Technical Field
The present invention relates to a device and technique for measuring viscosity and related properties of multiple samples, in some embodiments simultaneously, and is particularly useful for rapidly screening and characterizing a combinatorial library of materials.
2. Discussion
Combinatorial chemistry generally refers to methods and materials for creating collections of diverse materials or compoundsxe2x80x94commonly known as librariesxe2x80x94and to techniques and instruments for evaluating or screening libraries for desirable properties. Combinatorial chemistry has revolutionized the process of drug discovery, and has enabled researchers to rapidly discover and optimize useful materials.
One useful screening criterion is viscosity, xcex7, which is a physical property that characterizes a fluid""s resistance to flow. For laminar flow of Newtonian fluids, including gases and simple liquids, viscosity is proportional to the tangential component of stress (shear force) divided by the local velocity gradient. Although complex fluids such as pastes, slurries, and high polymers do not follow the simple relationship between tangential stress and local velocity gradient, viscosity and its analogs nevertheless can serve as useful screening criteria. For example, one can use viscosity measurements to estimate molecular weights of polymers in solution.
Combinatorial libraries routinely comprise hundreds or thousands of individual library members. As a result, most viscometers are unsuitable for screening purposes because they were designed to slowly process one sample at a time. Although generally the throughput of serial instruments and techniques can benefit from automation, many viscometers have relatively long response times, require time-consuming sample preparation, and exhibit sluggish temperature control, making such instruments impractical for use as screening tools.
The present invention overcomes, or at least mitigates, some or all the problems discussed above.
The present invention provides an apparatus for measuring viscosity or related properties of fluid samples in parallel. In some embodiments, the apparatus includes a plurality of tubes and reservoirs in fluid communication with the tubes. Each of the tubes has a predetermined length and a uniform inner diameter over at least a portion of the tube""s length. In addition, the tubes provide flow paths for the fluid samples, which are initially contained within the reservoirs. The apparatus also includes a mechanism for filling the reservoirs with the fluid samples, and a device for determining volumetric flow rates of fluid samples flowing from the reservoirs through the plurality of tubes simultaneously. The disclosed apparatus is capable of measuring viscosity or related properties of at least five fluid samples simultaneously.
The present invention also provides an apparatus comprised of an array of syringes for measuring viscosity or related properties of fluid samples in parallel. Each of the syringes includes a barrel for containing the fluid samples, a plunger located within the barrel for aspirating the fluid samples into the barrel, and a hypodermic needle in fluid communication with the barrel. The hypodermic needle, which has a substantially uniform diameter over a majority of its length, provides a flow path for the fluid samples. The apparatus also includes upstream and downstream detector arrays that are located along the barrel of each syringe. The detector arrays, which monitor volumetric flow rates of the fluid samples through each hypodermic needle, are capable of measuring viscosity or related properties of at least five fluid samples simultaneously.
Additionally, the present invention includes a method of screening fluid samples. The method comprises (1) providing fluid samples to a plurality of reservoirs; (2) allowing the fluid samples to flow from the reservoirs through a plurality of tubes; and (3) detecting the volumetric flow rates of at least five of the fluid samples through each of the tubes simultaneously.
Another embodiment of the present invention uses the same viscometer design with upstream and downstream detectors described above, but places at least one of those viscometers on tip of the arm of a three axis robot, and preferably at least two viscometers are placed on the tip of at least two arms of a three axis robot. In this embodiment, the viscometer is operated in the same manner described above and is moved from well to well of a sample tray or combinatorial library of samples. Many known liquid handling systems incorporate one or more tips and the viscometer may be placed on as many tips as are present in the robot being used. In addition, when multiple arm robots with multiple tips are used a high throughput instrument for viscosity measurements is provided. For example 8 tips on a 9 mm pitch may be provided on one or more arms of the robot. Thus, this embodiment of the present invention is either a rapid serial measurement or a simultaneous measurement on multiple samples.